NDM-1, the supergene: Further (community?) spread

Yesterday and today are early-publication days for the December issue of Emerging Infectious Diseases, the free peer-reviewed journal published by the Centers for Disease Control and Prevention. (Are you reading it? Why not? Your tax dollars pay for it. Go, now.) Among many interesting stories — more on those in later posts — there are two important, complex and saddening papers updating the relentless spread of the “Indian supergene,” New Delhi metallo-beta-lactamase or NDM-1.

(Pause for commentary: I hope we’ve put to rest by now the canard that naming this gene after New Delhi indicates some secret agenda to inflict stigma on the subcontinent’s burgeoning medical-tourism industry. It is a long-standing convention that the acquired metallo-beta-lactamases are named for their point of origin: Holland, Singapore, Germany, et al. You don’t see Vienna complaining, do you? ‘Nuf said.)

A brief recap, for those who spent August focused on something more interesting that bacterial resistance: NDM-1 is a gene that produces an enzyme that confers resistance on gram-negative bacteria to almost all the drugs used to treat them. The American Type Culture Collection, which sells isolates for research, recently published the table of resistance results, and it’s phenomenal: All Rs, all the way down. It was first identified in 2008 in a native of India, resident in Sweden, who had been hospitalized while on a visit back home; then found in the UK in 2009; and then found in the US in June this year. It renders bacteria that are common causes of hospital-acquired infections — Klebsiella, Acinetobacter, E. coli — resistant to all but one or two drugs. It’s extremely bad news. (My NDM-1 posts are here.)

It’s been clear since 2009 that NDM-1 is spreading around the world with great speed. The newest papers in EID confirm that and fill in the details — and wow, some of them are so sad.

First, from Austria: A team from the University Hospital in Graz reports that they have found NDM-1 in two patients separated by many months. The first was a 30-year-old man who had been taking a motorbike trip through South Asia and was badly injured in an accident in Pakistan: multiple fractures of his left leg and a rectal lacteration. He had surgery in hospitals in Pakistan, and then in India, and was transferred home. Once he got to the Austrian hospital, they found he had been infected during his South Asian treatment with multiple highly resistant bacteria, including a Klebsiella carrying NDM-1. He was hospitalized for five months while they tried various drug regimens and took him back and forth for reparative surgeries, and eventually recovered.

The second Austrian case demonstrates that NDM-1 cases no longer have a direct tie to South Asia. A 14-year-old boy from Kosovo was transferred to the Graz hospital in August this year. He needed critical care for infections he developed following a routine appendectomy in Pristina, Kosovo in April: He had peritonitis and multiple abscesses and draining fistulas scattered through his abdominal cavity. He was also carrying Klebsiella possessing NDM-1 — and, important ot note, he arrived with it, he did not pick it up from the hospital where the Austrian man had earlier been treated. He had no known connection to South Asia and had never traveled there. He is still in the hospital.

Second, and this story is both more sad and, in its implications, more scary: Researchers from the Public Health Agency of Canada and Vancouver General Hospital describe the case of a 76-year-old woman who was in India for 3.5 months and — completely normally for someone in rural India — developed diarrhea. The paper says nothing else about her, but we can infer just on those details that she must be fairly healthy. Or, rather, was — because here’s what happens next:

She doesn’t seek medical attention for the diarrhea, which is completely normal, since diarrhea is endemic in South Asia. But a month after it starts, her health becomes unexpectedly bad. She is hospitalized for high blood pressure and heart failure in India; treated and discharged after three days, and then goes back in to the hspital three days after that with a urinary tract infection, encephalitis and what the paper describes as a “decreased level of consciousness.” She is treated in the hospital for three weeks, does not improve, and so is medically evacuated back to Canada.

She arrives in septic shock. Within 24 hours, she’s in the ICU, ventilated, on vancomycin and imipenem, drugs of last resort for resistant gram-positive and gram-negative bacteria. They find that she is infected with highly resistant bacteria carrying NDM-1. Here’s where, for an epidemiologist, the dread starts creeping in: The bacteria possessing the resistance gene are not only Klebsiella, which people have come to expect, but also E. coli, a bug that, unlike Klebsiella, is not usually confined to hospitals, but exists freely in the outside world and in all of us. The implication, though no one can say for sure, is that the outside world — what public health calls “the community” — is where this woman picked up her infection. Remember, she fell ill before being hospitalized.

She is treated with multiple drug regimens. She does not improve. She is transferred out of the ICU to a general medical ward and dies several days later.

Yesterday, one of the authors, Dr. Michael Mulvey of the Public health Agency, announced that this woman was one of eight Canadians to be recognized with NDM-1 so far.